REGULATION OF CYCLIC NUCLEOTIDE METABOLISM

鸟嘌呤核苷酸结合蛋白是许多信号转导的关键元件， 动物细胞中的转导和代谢途径。其中一种蛋白质， ADP-核糖基化因子，基于其增强， GTP的存在，霍乱毒素的ADP-核糖基转移酶活性， 一种被认为在霍乱发病机理中起重要作用的反应。这些 研究与ARF作为一种 毒素的变构激活剂为了更详细地研究 在大肠杆菌中合成了ADP核糖基化因子重组蛋白。杆菌 重组ARF表现出高亲和力的鸟嘌呤核苷酸结合， 刺激霍乱毒素和E. 大肠杆菌不耐热肠毒素LT-I、LT-IIA和11 LT-IIB。急诊杆菌 先前显示热不稳定肠毒素催化酶促反应 与霍乱毒素类似的反应，并对 靶组织。霍乱毒素和E.大肠杆菌毒素表现出相当大的 结构保守，特别是在催化亚基中。这些 研究与以下结论一致，即催化活性 并且变构位点在毒素中是保守的。

Guanine nucleotide-binding proteins are critical elements in many signal transducing and metabolic pathways in animal cells. One of these proteins, ADP-ribosylation factor, was identified based on its ability to enhance, in the presence of GTP, the ADP-ribosyltransferase activity of cholera toxin, a reaction believed to be important in the pathogenesis of cholera. These studies were consistent with the conclusion that ARF serves as an allosteric activator of the toxin. To study in more detail the effects of ADP-ribosylation factor, a recombinant protein was synthesized in E. coli. The recombinant ARF exhibited high affinity guanine nucleotide-binding and stimulated the ADP-ribosyltransferase activities of cholera toxin and E. coli heat-labile enterotoxins LT-I, LT-IIA and 11 LT-IIB. The E. coli heat-labile enterotoxins were previously shown to catalyze enzymatic reactions similar to those of cholera toxin and to have similar effects on target tissues. Cholera toxin and the E. coli toxins exhibit considerable conservation in structure, particularly in the catalytic subunit. These studies are consistent with the conclusion that both the catalytic activity and the allosteric sites are conserved in the toxins.